Obese, Pre-diabetes, Weight Loss
Conditions
Keywords
Henagliflozin, Obese, Weight loss, Glucose
Brief summary
This trial is conducted in China. The purpose of the 24-week trial is to investigate the efficacy of henagliflozin to induce body weight loss and the purpose of the extension is to evaluate the hypoglycemic effect of henagliflozin in obese subjects without diabetes. Trial has the following two periods: 1) A 12-week randomized, double-blind, placebo-controlled, multi-center trial for evaluating the efficacy of henagliflozin to induce body weight loss; 2) A 12-week multicenter randomized controlled open-label trial for evaluating the hypoglycemic effect of henagliflozin followed by a 24-week extension period.
Detailed description
Primary Hypothesis: The 12-week henagliflozin taking could induce significantly higher weight loss in obese subjects without diabetes, compared to diet-exercise therapy. Assessment time points: Baseline: prior to taking henagliflozin or diet-exercise therapy V1: 4 weeks following the henagliflozin taking or diet-exercise therapy V2: 4 weeks following V1 V3: 4 weeks following V2 Specific Aims 1: To examine and compare the weight loss, assessed by weight, waist circumference, hip circumference and BMI, after 12-week henagliflozin taking or diet-exercise therapy in obese without diabetes. Specific Aims 2: To examine and compare the change of glucose level after 12-week henagliflozin taking or diet-exercise therapy in obese without diabetes. Secondary Hypothesis 1: The 24-week henagliflozin taking could siginificantly improve the glucose control in obese subjects with pre-diabetes, compared to diet-exercise therapy. Assessment time points: Baseline: prior to taking henagliflozin or diet-exercise therapy V4: 12 weeks following V3 Specific Aims: To examine and compare the change of glucose level, assessed by fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, insulin levels, after 24-week henagliflozin taking or diet-exercise therapy.
Interventions
DRUGHenagliflozin
10mg of Henagliflozin and diet-exercise therapy
DRUGPlacebo
Placebo and diet-exercise therapy
Sponsors
The Second Hospital of Nanjing Medical University
The First Affiliated Hospital of Soochow University
Second Affiliated Hospital of Soochow University
Wuxi People's Hospital
Northern Jiangsu People's Hospital
The Affiliated Hospital of Xuzhou Medical University
The First People's Hospital of Lianyungang
Affiliated Hospital of Jiangsu University
The fourth affiliated hospital of nantong university
The First People's Hospital of Changzhou
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
Participants and care providers are all masked. Investigators randomly cluster the participants, and the actual mask of the participant is not available to care providers and the participants
Intervention model description
Participants are randomly divided into two groups: control group and intervention group. In control group, Placebo and diet-exercise therapy is used. In intervention group, 10mg of henagliflozin and diet-exercise therapy is used.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 18 years old≤age≤65 years old, regardless of gender and race 2. Nondiabetic population: without hypoglycemic treatment, FPG\<7.0 mmol/l, PPG\<11.1 mmol/l, and HbA1c\<6.5% 3. obesity: BMI≥28 kg/m2 4. Stable weight: weight change less than 5kg in the past 3 months 5. Ability to understand and sign the informed consent form
Exclusion criteria
1. Allergies to Henagliflozin or its formulations; 2. Participants have been definitely diagnosed with diabetes; 3. HbA1c≥6.5 % or FPG≥7.0 mmol/l, or PPG≥11.1 mmol/l; 4. Participants have used glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose linked transporter-2 (SGLT-2) inhibitors, or other weight loss related drugs within the past 3 months; 5. History of bariatric surgery; 6. Untreated or uncontrolled hypothyroidism/hyperthyroidism; 7. High risk of urinary tract infection; 8. Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome); 9. Diagnosis of congenital glucose-galactose malabsorption or familial renal glycosuria 10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 times the upper limit of the normal range (UNL); Total bilirubin (TBIL) ≥ 2.0 times the upper limit of the normal range; 11. estimated glomerular filtration rate (eGFR)\<30 mL/min/1.73 m2 or end-stage kidney disease, or requiring dialysis; 12. History of major depressive disorder or other severe psychiatric disorders, e.g. schizophrenia, bipolar disorder within the last 2 years; 13. Uncontrolled treated/untreated hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg) 14. myocardial infarction, unstable angina, revascularization surgery, or cerebrovascular diseases within the past 3 months; 15. Cancer (past or present, except basal cell skin cancer or squamous cell skin cancer) or other severe diseases, which in the investigator's opinion could interfere with the results of the trial; 16. Females of child-bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) within 24 months; 17. Participation in a clinical trial within the last 3 months prior to screening; 18. Previous history of gestational diabetes; 19. Previous history of eating disorders; 20. Current or history of treatment with medications that may cause significant weight gain, within 3 months prior to screening, including systemic corticosteroids (except for a short course of treatment, i.e. 7-10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium); 21. Diet attempts using herbal supplements or over-the-counter medications within 3 months before screening 22. Any lifetime history of a suicidal attempt or a history of any suicidal behavior in the last month prior to randomization; 23. Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the investigator 24. Known or suspected abuse of alcohol or narcotics 25. Subjects from the same house hold participating in the trial 26. Other situations which were inappropriate to the trial, at the discretion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight change | 3 months (12 weeks) | Proportion of weight change from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of ≥5% weight loss | 3 months (12 weeks) | Proportion of patients who lost at least 5% of their body weight from baseline |
| Incident diabetes | 1 month (4 weeks), 2 months (8 weeks), 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks) | New-onset diabetes during follow up |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change of waist-to-hip ratio | 3 months (12 weeks) | Change of waist-to-hip ratio at the 3rd month. Waist-to-hip ratio will be defined as waist circumference (cm) to hip circumference (cm). |
| Change of FPG | 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks) | Change of FPG from baseline |
| Change of PPG | 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks) | Change of PPG from baseline |
| Changes of insulin levels | 3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks) | Changes of fasting and oral glucose tolerance test-2h insulin level from baseline |
| Changes of C-peptide levels | 3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks) | Changes of fasting and oral glucose tolerance test-2h C-peptide levels from baseline |
| Changes of HbA1c | 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks) | Changes of HbA1c levels from baseline |
| Absolute weight change | 3 months (12 weeks) | Absolute value of weight change from baseline for each group at the 3rd month |
| Changes of total cholesterol | 6 months (24 weeks), 12 months (48 weeks) | Changes in total cholesterol from baseline |
| Changes of LDL-c | 6 months (24 weeks), 12 months (48 weeks) | Changes in LDL-c from baseline |
| Changes of HDL-c | 6 months (24 weeks), 12 months (48 weeks) | Changes in HDL-c from baseline |
| Change of urinary albumin-to-creatinine ratio | 6 months (24 weeks), 12 months (48 weeks) | Change of urinary albumin-to-creatinine ratio from baseline in each group |
| Changes of C-reactive protein | 6 months (24 weeks), 12 months (48 weeks) | Changes of C-reactive protein in each group relative to baseline |
| Changes of triglyceride | 6 months (24 weeks), 12 months (48 weeks) | Changes in triglyceride from baseline |
| BMI change | 3 months (12 weeks) | Change in BMI from baseline for each group at the 3rd month. BMI was defined as weight (kg) divided by height squared (m2), weight and height will be combined to report BMI in kg/m\^2. |
| Change of waist circumference | 3 months (12 weeks) | Change of waist circumference at the 3rd month |
Contacts
Primary ContactFei Hua, PHD
Backup ContactXiaolin Huang, PHD
Outcome results
None listed